Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

Effect of cenobamate on the single-dose pharmacokinetics of multiple cytochrome P450 probes using a cocktail approach in healthy subjects.

This study was designed to evaluate the effects of cenobamate, an antiseizure medication for focal seizures, on the pharmacokinetics of cytochrome P450 probes (bupropion, CYP2B6; midazolam, CYP3A4/5; warfarin, CYP2C9; and omeprazole, CYP2C19) in healthy subjects. Probes were administered alone on days 1 (bupropion) and 7 (midazolam/warfarin/omeprazole), and with cenobamate 100 mg/day on day 69 (midazolam) and cenobamate 200 mg/day on days 99 (bupropion) and 105 (midazolam/warfarin/omeprazole). No significant interaction was concluded if 90% confidence intervals (CIs) for geometric mean ratios (GMRs) for area under the curve (AUC) and maximum concentration of CYP substrates and/or their metabolites were within the no-effect interval (0.80-1.25). When co-administered with cenobamate 100 mg/day, AUC from time of administration up to the time of the last quantifiable concentration (AUC0-last ) GMR (90% CIs) for midazolam was 0.734 (0.647-0.832). When co-administered with cenobamate 200 mg/day, AUC0-last GMRs (90% CI) for midazolam, bupropion, S-warfarin, and omeprazole were 0.277 (0.238-0.323), 0.615 (0.522-0.724), 1.14 (1.10-1.18), and 2.07 (1.44-2.98), respectively. Co-administration of cenobamate with midazolam and bupropion probes led to values that were outside and below the no effect boundary, indicating that cenobamate induces the CYP3A4/5 and CYP2B6 enzymes. Co-administration of cenobamate led to omeprazole values which were outside and above the no-effect boundary, but with high variability, suggesting that cenobamate may moderately inhibit CYP2C19 activity. No effect on CYP2C9 was observed with the cenobamate and warfarin combination. Co-administration of cenobamate with these probes drugs was well-tolerated. In this study, 200 mg/day cenobamate moderately induced CYP3A4/5 (dose-dependently; 100 mg/day was a weak inducer), was a weak inducer of CYP2B6, moderately inhibited CYP2C19, and had a negligible effect on CYP2C9.

Mass Balance, Metabolism, and Excretion of Cenobamate, a New Antiepileptic Drug, After a Single Oral Administration in Healthy Male Subjects.

BACKGROUND AND OBJECTIVE: Cenobamate is an antiepileptic drug for the treatment of partial-onset seizures. The current study was designed to assess the mass balance and the metabolic profiling of cenobamate in humans. METHODS: Absorption, metabolism, and excretion of cenobamate were investigated in healthy male subjects after a single oral dose of 400 mg of cenobamate containing 50 µCi of [14C]-cenobamate as capsule formulation. RESULTS: Cenobamate was rapidly (median time to maximum plasma concentration of 1.25 h) and extensively (≥ 88% of dose) absorbed. The mean cenobamate plasma concentration-time profile revealed a multiphasic elimination profile whereas the mean plasma/blood concentration-time curve for total radioactivity did not appear to be multiphasic, suggesting that elimination mechanisms for cenobamate and its metabolites may be different. Blood/plasma ratios observed for the area under the concentration-time curve (AUC) and peak concentration (both ~ 0.60) suggest a limited penetration of cenobamate and metabolites into red blood cells (RBCs). Eight cenobamate metabolites were identified across plasma, urine, and feces. Cenobamate was the main plasma radioactive component and M1 was the only metabolite detected in plasma (> 98% and < 2% total radioactivity AUC, respectively). All detected metabolites were found in urine, with M1 as the major radioactive component (mean cumulative recovery 37.7% of dose); unchanged cenobamate accounted for 6%. Metabolites comprised ~ 88% of the dose recovered in urine, indicating extensive metabolism by the kidneys and/or metabolites formed in the liver were rapidly eliminated from the bloodstream. However, cenobamate metabolites appear to be formed slowly. Minor amounts of cenobamate (0.48%) and five metabolites (≤ 1.75% each; M1, M3, M6, M7, M11) were recovered in feces. CONCLUSION: This study indicates that cenobamate is primarily eliminated in urine as metabolites. Cenobamate is the major circulating component in plasma after oral administration and has a limited penetration into RBCs.

The association of benign prostatic hyperplasia with lower urinary tract stones in adult men: A retrospective multicenter study.

OBJECTIVE: To examine the relationship between benign prostatic hyperplasia (BPH) and the presence of lower urinary tract stones. METHODS: We retrospectively reviewed the records of men with lower urinary tract stones who presented to three clinical centers in Korea over a 4-year period. We divided the patients into two groups based on the location of urinary stones: Group 1 (bladder calculi) and Group 2 (urethral calculi). We compared the characteristics of both groups and performed univariate and multivariate analyses with a logistic regression model to investigate the relationship between BPH and lower urinary tract stones. RESULTS: Of 221 patients, 194 (87.8%) had bladder calculi and 27 (12.2%) had urethral calculi. The mean age of Group 1 was higher than that of Group 2 (68.96 ± 12.11 years vs. 55.74 ± 14.20 years, p < 0.001). The mean prostate volume of Group 1 was higher than that of Group 2 (44.47 ± 27.14 mL vs. 24.70 ± 6.41 mL, respectively, p < 0.001). Multivariate logistic regression showed that age (OR = 1.075, 95%CI: 1.023-1.129) and prostate volume (OR = 1.069, 95%CI: 1.017-1.123) were independently associated with increased risk for bladder calculi. Upper urinary tract stones and/or hydronephrosis conferred a 3-fold risk for urethral calculi (OR = 3.468, 95%CI: 1.093-10.999). CONCLUSION: Age and prostate volume are independent risk factors for bladder calculi. In addition, men with upper urinary tract disease are at greater risk for urethral calculi, which may migrate from the upper urinary tract rather than from the bladder.

Feasibility of Transvesical Robotic VVF Repair in Porcine Model.

Extraperitoneal transvesicoscopic vesicovaginal fistula (VVF) repair has received limited use because of its narrow working space, longer operation time, and technical difficulty. The present study describes the feasibility of robotic-assisted transvesicoscopic VVF repair in an animal model. Two Yorkshire swine underwent robotic-assisted laparoscopic (RAL) VVF repair. With the 4 trocars, an artificial VVF was made in the supratrigonal area and VVF repair was performed in 3 layers as in open VVF repair methods. The mean operation time was 108 minutes. The operation time was prolonged in 1 case due to weak fixation of bladder to anterior abdominal wall. Equipment interference did not occur. Tissue manipulation and suturing were easy. The results of this study suggest that extraperitoneal RAL procedures for VVF repair may be an effective minimally invasive modality with reduced morbidity. A shorter operation time and easy suturing technique were the distinct merits of the extraperitoneal RAL technique.

Prokinetic effects of a new 5-HT4 agonist, YKP10811, on gastric motility in dogs.

BACKGROUND AND AIM: Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT4 receptor agonist, YKP10811, on gastric motility in dogs. METHODS: Four experiments were performed in dogs: (i) dose-response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation. RESULTS: No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation. CONCLUSIONS: YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis.

The Effectiveness of Silodosin for Nocturnal Polyuria in Elderly Men With Benign Prostatic Hyperplasia: A Multicenter Study.

PURPOSE: To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. METHODS: This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to the study protocol (per-protocol group), and 24 dropped out (dropout group). RESULTS: Of the 24 patients in the dropout group, 5 withdrew consent due to side effects or lack of efficacy, 7 were lost to follow-up at 4 weeks, 8 were lost to follow-up at 12 weeks, and 4 dropped out due to failure to complete 3-day frequency volume charts at 12 weeks. In the per-protocol group, there was significant improvement in the International Prostate Symptom Score (IPSS), especially question numbers 1, 3, 4, 5, 6, 7, and the quality of life question (P=0.001, P=0.007, P<0.001, P=0.003, P=0.049, P<0.001, and P<0.001, respectively). The Leeds sleep evaluation questionnaire (LSEQ) score for the sleep question improved from 64.36 to 70.43 (P=0.039). The NPi reduced from 0.4005 to 0.3573 (P=0.027); however, in many cases, there was no improvement in nocturnal polyuria itself. In intention-to-treat analysis, there were significant improvements in IPSS and LSEQ in 45 patients. CONCLUSIONS: In elderly nocturnal polyuria patients, silodosin monotherapy exhibits good efficacy in improving nocturia and nocturnal polyuria; however, the mean NPi was still >0.33. Considering the high dropout rate of our study due to no implementation of 3-day frequency volume charts, prospective and large-scale studies are needed to confirm our results.

Distribution of ureteral stones and factors affecting their location and expulsion in patients with renal colic.

PURPOSE: To evaluate the distribution of ureteral stones and to determine their characteristics and expulsion rate based on their location. MATERIALS AND METHODS: We retrospectively reviewed computed tomography (CT) findings of 246 patients who visited our Emergency Department (ED) for renal colic caused by unilateral ureteral stones between January 2013 and April 2014. Histograms were constructed to plot the distribution of stones based on initial CT findings. Data from 144 of the 246 patients who underwent medical expulsive therapy (MET) for 2 weeks were analyzed to evaluate the factors responsible for the stone distribution and expulsion. RESULTS: The upper ureter and ureterovesical junction (UVJ) were 2 peak locations at which stones initially lodged. Stones lodged at the upper ureter and ureteropelvic junction (group A) had a larger longitudinal diameter (4.21 mm vs. 3.56 mm, p=0.004) compared to those lodged at the lower ureter and UVJ (group B). The expulsion rate was 75.6% and 94.9% in groups A and B, respectively. There was no significant difference in the time interval from initiation of renal colic to arrival at the ED between groups A and B (p=0.422). Stone diameter was a significant predictor of MET failure (odds ratio [OR], 1.795; p=0.005) but the initial stone location was not (OR, 0.299; p=0.082). CONCLUSIONS: The upper ureter and UVJ are 2 peak sites at which stones lodge. For stone size 10 mm or less, initial stone lodge site is not a significant predictor of MET failure in patients who have no previous history of active stone treatment in the ureter.

Comparison of treatment outcomes according to output voltage during shockwave lithotripsy for ureteral calculi: a prospective randomized multicenter study.

PURPOSE: To investigate the effect of fixed versus escalating voltage during SWL on treatment outcomes in patients with ureteral calculi (UC). METHODS: A prospective, randomized, multicenter trial was conducted on 120 patients who were diagnosed with a single radiopaque UC. The patients were randomized into group C (n = 60, constant 13 kV, 3,000 shock wave, 2 Hz) or group E (n = 60, 11.4-12.0-13 kV per 1,000 shock waves, 2 Hz). They were evaluated by plain abdominal radiography and urinalysis at 1 week after a single session of SWL, and repeat SWL was performed if needed. The primary endpoint was stone-free rate at 1 week (SFR1) after SWL. Secondary endpoints were post-SWL visual pain score (VPS), oral analgesic requirements during 1 week, and cumulative SFRs after the second and third sessions of SWL. RESULTS: Groups C and E were well balanced in terms of baseline patients and stone characteristics, including pre-SWL VPS, stone location, and stone size (6.24 ± 1.92 vs. 6.30 ± 2.13 mm). SFR1s were not significantly different between groups C and E (60.0 vs. 68.3%, p = 0.447). Analyses stratified by stone size (<6 vs. ≥6 mm) showed no difference in SFR1 (p = 0.148 vs. 0.808). In the analyses stratified by stone location, group E tended to be more effective in distal UC (81.0 vs. 50.0%, p = 0.052), whereas no difference was seen in proximal UC (p = 0.487). Secondary endpoints were also similar between the two groups. CONCLUSIONS: Our results suggest that voltage escalation during SWL in UC may not provide superior stone fragmentation compared to fixed voltage.

Clinical application of computed tomography on prostate volume estimation in patients with lower urinary tract symptoms.

PURPOSE: To compare estimated prostate volume (PV) based on computed tomography (CT) scan and transrectal ultrasonography (TRUS) in patients with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Between January 2010 and October 2012, 107 consecutive patients with LUTS were analyzed, retrospectively. PV measures were performed by the means of ellipsoid formula (PV = π/6 [width (cm) thick­ness (cm) length (cm)]) from TRUS (PVTRUS) and CT (PVCT ellipsoid). In addition, PV was calculated as the sum of the area of each slice and the CT slice interval using commercial software program (PVCT 3D reconstruction). RESULTS: Mean PVCT ellipsoid was 40.63 & plusmn; 31.06 cm3 (range, 8.34-217.46). Mean PVTRUS and PVCT 3D reconstruction were 39.20 & plusmn; 33.04 (range, 4.00-223.81) and 45.30 & plusmn; 32.98 (range, 8.90-248.30), respectively. PVCT ellipsoid was highly correlated with PVTRUS and PVCT 3D reconstruction (r = 0.935, P < .001; r = .970, P < .001, respectively). Moreover, there was very strong agreement for PV measurements with all three methods (intraclass correlation coefficient = 0.934, P < .001). CONCLUSION: PVCT ellipsoid is adequate method for quick volume assessment with reasonable accuracy. Therefore, we can easily predict PV by CT scan using ellipsoid formula without performing additional TRUS in patients with LUTS.& nbsp;

Clinical Outcomes of CyberKnife Radiotherapy in Prostate Cancer Patients: Short-term, Single-Center Experience.

PURPOSE: In this retrospective study, we analyzed the outcomes of prostate cancer patients treated with the CyberKnife radiotherapy system (Accuray). MATERIALS AND METHODS: Between 2007 and 2010, 31 patients were treated for prostate cancer by use of the CyberKnife radiotherapy system. After excluding six patients who were lost to follow-up, data for the remaining 25 patients were analyzed. Patients were divided into the CyberKnife monotherapy group and a postexternal beam radiotherapy boost group. Clinicopathologic features and treatment outcomes were compared between the groups. The primary endpoint was biochemical recurrence-free survival period based on the Phoenix definition. Toxicities were evaluated by using the Radiation Therapy Oncology Group scoring criteria. RESULTS: Of 25 patients, 17 (68%) and 8 (32%) were classified in the monotherapy and boost groups, respectively. With a median follow-up of 29.3 months, most of the toxicities were grade 1 or 2 except for one patient in the boost group who experienced late grade 3 gastrointestinal toxicity. The overall biochemical recurrence rate was 20% (5/25) and the median time to biochemical recurrence was 51.9 months. None of the patients with low or intermediate risk had experienced biochemical recurrence during follow-up. Among D'Amico high-risk populations, 16.7% (1/6) in the monotherapy group and 50.0% (4/8) in the boost group experienced biochemical recurrence. CONCLUSIONS: Our data support that prostate cancer treatment by use of the CyberKnife radiotherapy system is feasible. The procedure can be a viable option for managing prostate cancer either in a monotherapy setting or as a boost after conventional radiotherapy regardless of the patient's risk stratification.

Simultaneous robot-assisted laparoendoscopic single-site partial nephrectomy and standard radical prostatectomy.

Recently, patients with urologic malignancies are treated with robot-assisted surgery and the expanded role of robot-assisted surgery includes even those patients with two concomitant primary urologic malignancies. In an effort to further reduce port site-related morbidity, robot-assisted laparoendoscopic single-site surgery (RLESS) has been developed. Therefore, we present herein our early experience and feasibility of simultaneous RLESS partial nephrectomy and standard robotrobot- assisted laparoendoscopic radical prostatectomy (RALP) on 3 patients with synchronous renal masses and prostate cancer.

Prostatic urethral angulation associated with urinary flow rate and urinary symptom scores in men with lower urinary tract symptoms.

OBJECTIVE: To evaluate the effect of the prostatic urethral angle (PUA) on the peak flow rate (Qmax) and urinary symptoms in the clinical setting. MATERIALS AND METHODS: The records were obtained from a prospectively maintained database for first-visit men with lower urinary tract symptoms. Uroflowmetric measurements, postvoid residual urine volume, and International Prostate Symptom Score were assessed. The prostate-related parameters, including prostate volume, PUA, and intravesical prostatic protrusion, were measured using transrectal ultrasonography. Patients with comorbidities that can affect voiding function or in whom the PUA could not be measured were excluded. RESULTS: A total of 316 patients were included. On multivariate linear regression analysis, the PUA (P = .002) was independently associated with the International Prostate Symptom Score. However, the International Prostate Symptom Score was not influenced by patient age, prostate volume, or intravesical prostatic protrusion. The mean PUA was significantly different according to symptom severity. The mean PUA was 42.2° ± 7.0°, 45.5° ± 9.1°, and 47.3° ± 8.6° in patients with mild, moderate, and severe symptoms, respectively (P = .004, analysis of variance). Although the PUA (P <.001) and patient age (P <.001) were independent predictors of Qmax, the prostate volume and intravesical prostatic protrusion did not affect the Qmax. The mean PUA was 52.2° ± 7.3° in patients with a Qmax <10 mL/s, 45.0° ± 7.9° in those with a Qmax ≥10 mL/s but <20 mL/s, and 39.8° ± 7.9° in those with a Qmax of ≥20 mL/s (P <.001, analysis of variance). CONCLUSION: The results of our study has shown that the PUA is significantly associated with the Qmax and symptom scores in men with lower urinary tract symptoms. Our findings suggest that the PUA should be considered in the treatment of male patients with lower urinary tract symptoms.

Discrepancies in perception of urinary incontinence between patient and physician after robotic radical prostatectomy.

PURPOSE: Reported incidence of urinary incontinence after a radical prostatectomy (RP) varies between studies. This may be due not only to the definition of incontinence applied, but also how the information is acquired. We investigated the differences in perception of post robot-assisted laparoscopic RP (RALP) urinary incontinence acquired through doctor interviews and patient-reported questionnaires. MATERIALS AND METHODS: Of 238 consecutive men who underwent RALP by a single surgeon between July 2005 and February 2008, we evaluated 66 men using the International Consultation on Incontinence Questionnaire (ICIQ) at various time points after surgery. Each patient's ICIQ results were considered to be the patient's perceptions of urinary incontinence. The physician at the same time directly interviewed the patients about the number of pads used and considered complete continence to be equivalent to the use of no pads or safety liners. RESULTS: Of the 66 patients, the physician reported that 34 (51.5%) had obtained complete continence. However, analysis of the questionnaires of these 34 patients revealed that only 5 (14.7%) patients reported that they never leaked during the past 4 weeks. Most patients (11 patients, 32.4%) who did not use any pad did in fact reported leakage of a small or moderate amount of urine about once a day. CONCLUSION: Our results indicate that there are discrepancies in the perception of urinary incontinence between doctor and patient after RALP. Nonuse of pads is not equivalent to obtaining complete urinary continence. Therefore, the number of pads used is not a good measure to determine the status of complete urinary continence.

Astaxanthin uptake in domestic dogs and cats.

BACKGROUND: Research on the uptake and transport of astaxanthin is lacking in most species. We studied the uptake of astaxanthin by plasma, lipoproteins and leukocytes in domestic dogs and cats. METHODS: Mature female Beagle dogs (18 to 19 mo old; 11 to 14 kg BW) were dosed orally with 0, 0.1, 0.5, 2.5, 10 or 40 mg astaxanthin and blood taken at 0, 3, 6, 9, 12, 18 and 24 h post-administration (n = 8/treatment). Similarly, mature domestic short hair cats (12 mo old; 3 to 3.5 kg body weight) were fed a single dose of 0, 0.02, 0.08, 0.4, 2, 5, or 10 mg astaxanthin and blood taken (n = 8/treatment) at the same interval. RESULTS: Both dogs and cats showed similar biokinetic profiles. Maximal astaxanthin concentration in plasma was approximately 0.14 mumol/L in both species, and was observed at 6 h post-dosing. The plasma astaxanthin elimination half-life was 9 to 18 h. Astaxanthin was still detectable by 24 h in both species. In a subsequent study, dogs and cats were fed similar doses of astaxanthin daily for 15 to 16 d and astaxanthin uptake by plasma, lipoproteins, and leukocytes studied. In both species, plasma astaxanthin concentrations generally continued to increase through d 15 or 16 of supplementation. The astaxanthin was mainly associated with high density lipoprotein (HDL). In blood leukocytes, approximately half of the total astaxanthin was found in the mitochondria, with significant amounts also associated with the microsomes and nuclei. CONCLUSION: Dogs and cats absorb astaxanthin from the diet. In the blood, the astaxanthin is mainly associated with HDL, and is taken up by blood leukocytes, where it is distributed to all subcellular organelles. Certain aspects of the biokinetic uptake of astaxanthin in dogs and cats are similar to that in humans.